The long term objective os this laboratory is to identify nutritional factors which contribute to the high incidence of colon cancer in Western culture. Diets high in cholesterol or drugs which increase cholesterol disbursement through the gut are all associated with increased tumorigenesis of the large bowel. Both clinical and epidemiologic studies indicate an increased disbursement of cholesterol into the colon in individuals at high risk for colon cancer compared to those at lower risk. Studies in rats from this laboratory have shown that dietary cholesterol augments both 1,2,-dimethylhydrazine and N-methyl-N-nitrosura (MNU) induced colon tumorigensis. These effects are manifest during the initiation or early promotional phase of MNU induced tumorigenesis. Planned, are studies to more precisely define the stage of action of dietary cholesterol. Cholesterol feeding, in preliminary studies, was observed to increase cholesterol uptake from serum and cholesterol content of MNU induced colonic tumors and adjacent colonic tissue. Cholesterol and fatty acid synthesis appears to be greater in the latter and was not influenced by dietary cholesterol in either. Planned is a continuation of this work. Correlative studies are also included to ascertain if the increased cholesterol content of the colonic mucosa resulting from cholesterol feeding serves to 1) disburse cholesterol into the bowel lumen; 2) influence colonic epithelial cell turnover; and 3) enhance the permeability of the colon to the "absorption" of a direct acting alkylating agent MNU. It is anticipated that these studies will provide 1) a better understanding of the relationship among nutrition gut microflora and colon cancer; 2) nutritional guidelines aimed at the prevention of colon cancer; and 3) guidelines for nutritional intervention in conjunction with radiatio, chemotherapy and immunotherapy in the managment of the patient with the colon cancer.